Chronic diseases related to immune responses include rheumatoid arthritis and other autoimmune diseases (systemic lupus erychematosus, psoriatic arthritis, atopic dermatitis, ankylosing spondylitis). These diseases are considered to be caused by bacteria, virus or autoantigens or by an aberration in cytokine regulation of T cells. Especially, patients with rheumatoid arthritis demonstrate various immune abnormalities including reduced functions of suppressor T cells and hyperactivity of B cells.
Non-steroidal antiinflammatory drugs are widely used as first choice drugs in the therapy of rheumatoid arthritis and other diseases due to immunological disorders. While these drugs offer symptomatic relief for patients with these diseases, they fail to alter the underlying immunological dysfunction or the overall course of the disease process. Furthermore, serious side effects from prolonged use of these drugs also have been well documented.
On the other hand, second choice antirheumatic drugs, such as gold salt and D-penicillamine have little acute antiinflammatory effects, but they appear to slow or halt the tissue destruction and more especially the progression of articular damage. They also have immunomodulatory effects. However, it is necessary to improve the safety and other aspects of these drugs, because of the higher incidence of side effects that have been observed in 40-50% of the patients treated with these drugs.
Metabolic bone diseases as generic term include osteoporosis, osteomalacia and ostetic fibrous. In patients with the diseases, there are morbid changes in weight, constitution and structure of bone as a result of the failure of the systemic bone formation and resorption process. This is caused by abnormalities in the somatological regulatory system due to various hormones or vitamins and by congenital or acquired abnormalities of the functions of the osteocytes. It is also associated with abnormal calcium and phosphorus metabolism. Vitamin D, calcium, calcitonin and phosphorus are used as therapeutic drugs, but their effectiveness has not been clearly proven and development of a superior drug has been strongly desired.